Calprotectin is a heterodimeric protein which belongs to the calcium-binding protein S100 family. Calprotectin is released by leukocytes at the site of inflammation and it can be detected in the feces where it remains stable for about a week. Hence, increased fecal calprotectin (FC) levels are found in several inflammatory conditions, mainly the inflammatory bowel diseases (IBD). In the setting of pediatric gastroenterology, the importance of FC has increased over time. This review aims to summarize the most recent findings concerning the role of FC in the algorithm of different inflammatory and non-inflammatory conditions among pediatric patients. Increasing evidences support the use of this biomarker for diagnosis, follow-up and evaluation of response to therapy of several pediatric gastrointestinal diseases, ranging from IBD to lymphocytic/ eosinophilic/ and nonspecific colitis and necrotizing enterocolitis. More efforts should be done to clarify the optimal cut-off of FC levels in patients younger than 5 years.